Neural stimulation systems, devices and methods

ABSTRACT

Various system embodiments comprise circuitry to determine when an arrhythmia has terminated, and a neural stimulator adapted to temporarily deliver neural stimulation therapy to assist with recovering from the arrhythmia in response to termination of the arrhythmia.

CLAIM OF PRIORITY

This application is a division of U.S. application Ser. No. 11/610,234,filed Dec. 13, 2006, now issued as U.S. Pat. No. 8,706,212, which ishereby incorporated by reference in its entirety.

FIELD

This application relates generally to medical devices and, moreparticularly, to systems, devices and methods for providing neuralstimulation therapy.

BACKGROUND

Neural stimulation has been the subject of a number of studies and hasbeen proposed for several therapies. Direct electrical stimulation ofparasympathetic nerves can activate the baroreflex, inducing a reductionof sympathetic nerve activity and reducing blood pressure by decreasingvascular resistance. Sympathetic inhibition, as well as parasympatheticactivation, have been associated with reduced arrhythmia vulnerabilityfollowing a myocardial infarction, presumably by increasing collateralperfusion of the acutely ischemic myocardium and decreasing myocardialdamage. Modulation of the sympathetic and parasympathetic nervous systemwith neural stimulation has been shown to have positive clinicalbenefits, such as protecting the myocardium from further remodeling andpredisposition to fatal arrhythmias following a myocardial infarction.

SUMMARY

Various system embodiments comprise circuitry to determine when anarrhythmia has terminated, and a neural stimulator adapted totemporarily deliver a neural stimulation therapy to assist withrecovering from the arrhythmia in response to termination of thearrhythmia. Various method embodiments comprise determining that anarrhythmia has terminated and temporarily delivering a neuralstimulation therapy to assist with recovering from the arrhythmia upontermination of the arrhythmia. Various method embodiments comprisechronically performing a prophylactic neural stimulation therapy,temporarily delivering an arrhythmia therapy, an apnea therapy, or apain therapy in response to a therapy trigger, and chronicallyperforming the prophylactic neural stimulation therapy upon completionof the arrhythmia therapy, the apnea therapy or the pain therapy.Various method embodiments comprise delivering a pretherapy stimulationin preparation for delivering a therapy in response to a therapytrigger, delivering the therapy, and delivering a post-therapy neuralstimulation to assist with recovering from the therapy upon completionof delivering of the therapy.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects will be apparent to persons skilled in the art upon reading andunderstanding the following detailed description and viewing thedrawings that form a part thereof, each of which are not to be taken ina limiting sense. The scope of the present invention is defined by theappended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a therapy time line where prophylactic neuralstimulation is interrupted for a temporary neural stimulation therapy,according to various embodiments.

FIG. 2 illustrates a therapy time line where pre-therapy andpost-therapy stimulations are delivered, according to variousembodiments.

FIG. 3 illustrates a therapy time line where pre-therapy and multi-stagepost-therapy stimulations are delivered, according to variousembodiments.

FIG. 4 illustrates a therapy time line where prophylactic neuralstimulation is interrupted to provide a pre-therapy stimulation, atherapy, and a multi-stage post-therapy stimulation, according tovarious embodiments.

FIG. 5 illustrates a therapy time line where post-arrhythmia therapy isdelivered, according to various embodiments.

FIG. 6 illustrates a therapy time line where prophylactic neuralstimulation is interrupted by post-arrhythmia therapy, according tovarious embodiments.

FIG. 7 illustrates a therapy time line where a multi-stagepost-arrhythmia therapy is delivered, according to various embodiments.

FIG. 8 illustrates a therapy time line where prophylactic neuralstimulation is interrupted by multi-stage post-arrhythmia therapy,according to various embodiments.

FIG. 9 illustrates a therapy time line where prophylactic neuralstimulation is interrupted to deliver a pre-therapy stimulation, atherapy for an arrhythmia, and a multi-stage post arrhythmiastimulation, according to various embodiments.

FIGS. 10-13 illustrate flow diagrams of processes for deliveringpost-arrhythmia vagus nerve modulation (VNM), according to variousembodiments.

FIG. 14 illustrates an implantable medical device (IMD), according tovarious embodiments.

FIG. 15 illustrates an implantable medical device (IMD) having a neuralstimulation (NS) component and a cardiac rhythm management (CRM)component according to various embodiments.

FIG. 16 shows a system diagram of an embodiment of amicroprocessor-based implantable device, according to variousembodiments.

FIG. 17 illustrates a system embodiment in which an IMD is placedsubcutaneously or submuscularly in a patient's chest with lead(s)positioned to stimulate a vagus nerve.

FIG. 18 illustrates a system embodiment that includes an implantablemedical device (IMD) with satellite electrode(s) positioned to stimulateat least one neural target.

FIG. 19 illustrates an IMD placed subcutaneously or submuscularly in apatient's chest with lead(s) positioned to provide a CRM therapy to aheart, and with lead(s) positioned to stimulate and/or inhibit neuraltraffic at a neural target, such as a vagus nerve, according to variousembodiments.

FIG. 20 illustrates an IMD with lead(s) positioned to provide a CRMtherapy to a heart, and with satellite transducers positioned tostimulate/inhibit a neural target such as a vagus nerve, according tovarious embodiments.

FIG. 21 illustrates an embodiment of a responsive relationship of an IMDcontroller to a triggering event.

FIG. 22 illustrates an embodiment of a controller capable of switchingmodes within a set of operation modes, a set of stimulation site modes,and a set of feedback modes.

DETAILED DESCRIPTION

The following detailed description of the present subject matter refersto the accompanying drawings which show, by way of illustration,specific aspects and embodiments in which the present subject matter maybe practiced. These embodiments are described in sufficient detail toenable those skilled in the art to practice the present subject matter.Other embodiments may be utilized and structural, logical, andelectrical changes may be made without departing from the scope of thepresent subject matter. References to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.The following detailed description is, therefore, not to be taken in alimiting sense, and the scope is defined only by the appended claims,along with the full scope of legal equivalents to which such claims areentitled.

Various neural stimulation device embodiments switch between or amongneural stimulation modes upon an internal and/or external trigger.Different neural stimulation modes are distinct from each other in oneor more ways, such as different stimulation signal amplitudes, differentstimulation frequencies, different pulse widths, different duty cycles,different directionality (unidirectional in afferent direction,unidirectional in efferent direction, or bidirectional in both afferentand efferent directions), different neural stimulation schedules,different neural stimulation duration, different stimulationlocation(s), and/or different feedback parameter(s) for closed-loopsystem embodiments.

Various embodiments switch modes for a transitory period of time inresponse to the application of a defibrillatory shock or in response toanother temporary condition such as an atrial or ventricular arrhythmia(including tachycardia or bradycardia), or apnea, or pain (includingprophylactic or preventative neural stimulation such as stimulation foranticipated pain associated with an antitachycardia shock, ortherapeutic stimulation such as stimulation for migraine or anginapain).

As some embodiments pertain to therapies associated with antitachycardiashocks, a brief discussion of tachycardia is provided herein. The heartis the center of a person's circulatory system. The left portions of theheart draw oxygenated blood from the lungs and pump it to the organs ofthe body to provide the organs with their metabolic needs for oxygen.The right portions of the heart draw deoxygenated blood from the bodyorgans and pump it to the lungs where the blood gets oxygenated.Contractions of the myocardium provide these pumping functions. In anormal heart, the sinoatrial node, the heart's natural pacemaker,generates electrical impulses that propagate through an electricalconduction system to various regions of the heart to excite themyocardial tissues of these regions. Coordinated delays in thepropagations of the electrical impulses in a normal electricalconduction system cause the various portions of the heart to contract insynchrony, which efficiently pumps the blood. Blocked or abnormalelectrical conduction or deteriorated myocardial tissue causesdysynchronous contraction of the heart, resulting in poor hemodynamicperformance, including a diminished blood supply to the heart and therest of the body. Heart failure occurs when the heart fails to pumpenough blood to meet the body's metabolic needs. Tachyarrhythmias areabnormal heart rhythms characterized by a rapid heart rate. Examples oftachyarrhythmias include supraventricular tachycardias (SVT's) such asatrial tachycardia (AT) and atrial fibrillation (AF), and the moredangerous ventricular tachyarrhythmias which include ventriculartachycardia (VT) and ventricular fibrillation (VF). Abnormal ventricularrhythms occur when re-entry of a depolarizing wavefront in areas of theventricular myocardium with different conduction characteristics becomesself-sustaining or when an excitatory focus in the ventricle usurpscontrol of the heart rate from the sinoatrial node. The result is rapidand ineffective contraction of the ventricles out of electromechanicalsynchrony with the atria. Many abnormal ventricular rhythms exhibit anabnormal QRS complex in an electrocardiogram because the depolarizationspreads from the excitatory focus or point of re-entry directly into themyocardium rather than through the normal ventricular conduction system.Ventricular tachycardia is typically characterized by distorted QRScomplexes that occur at a rapid rate, while ventricular fibrillation isdiagnosed when the ventricle depolarizes in a chaotic fashion with noidentifiable QRS complexes. Both ventricular tachycardia and ventricularfibrillation are hemodynamically compromising, and both can belife-threatening. Ventricular fibrillation, however, causes circulatoryarrest within seconds and is the most common cause of sudden cardiacdeath. Cardioversion, electrical shock delivered to the heartsynchronously with the QRS complex, and defibrillation, an electricalshock delivered without synchronization to the QRS complex, can be usedto terminate most tachyarrhythmias. Cardioversion and defibrillation arereferred generally herein as antitachycardia shocks. The electric shockterminates the tachyarrhythmia by simultaneously depolarizing themyocardium and rendering it refractory. A class of cardiac rhythmmanagement (CRM) devices known as an implantable cardioverterdefibrillator (ICD) provides this kind of therapy by delivering a shockpulse to the heart when the device detects tachyarrhythmias. One type ofelectrical therapy for tachycardia is antitachycardia pacing (ATP). Inventricular ATP, the ventricles are competitively paced with one or morepacing pulses in an effort to interrupt the reentrant circuit causingthe tachycardia. Modern ICDs typically have ATP capability, and deliverATP therapy or a shock pulse when a tachyarrhythmia is detected.

Various embodiments switch modes for a transitory period of time duringthe charge period in preparation for a shock. Neural stimulation therapymay be reduced or withdrawn during the post-shock period. Neuralstimulation therapy may switch from chronic, low-duty-cycle heartfailure therapy to a temporary, high-duty-cycle neural stimulationtherapy for pain minimization. The mode switch trigger may occur inresponse to an internal trigger or in response to a detected event (suchas the detection of defibrillatory energy in a stand alone neuralstimulation device). Various embodiments wait an intershock period (e.g.10 to 30 seconds) to determine that the antitachycardia shock wassuccessful.

Various device embodiments revert back to a chronic stimulation modeafter a transitory period, such as a period within a range ofapproximately 10 to 100 minutes, for example. The transitory period oftime can be terminated by arrhythmia cessation, arrhythmia progression(e.g. VT to VF), arrhythmia cessation plus a predetermined time intervalor a predetermined number of heart beats or respiration cycles, etc.,arrhythmia initiation predetermined time interval or a predeterminednumber of heart beats or respiration cycles, etc., and/or a change in aphysiological parameter (blood pressure, conduction time, catecholaminelevel, etc.). The time period can be based on time, a detected end tothe condition, heart beats, and end of an event plus a time interval, ora trigger based on a physiologic event.

Various embodiments employ neural stimulation for treating the cardiacsystem in response to and after an arrhythmic event. The neuralstimulation may be independent or used in conjunction with othertreatments such as bradycardia pacing.

Various device embodiments are programmed and otherwise adapted todetermine an arrhythmia-ending event and subsequently alter treatment ofthe cardiac system with neuromodulation therapy. In various embodiments,for example, a device is programmed to deliver therapies in response todetection of a post-atrial arrhythmia and withdraw therapies in responseto detection of a high-voltage defibrillation shock.

The implanted device can be an independent neuromodulation therapysystem, a neuromodulation therapy system cooperating with anotherimplanted medical device, or a combined neuromodulation therapy withother functionality such as those typically found in implantedpacemakers and defibrillators. An arrhythmia-ending event can be theresult of a non-sustained atrial or ventricular arrhythmia, anarrhythmia converted via drug cardioversion, an arrhythmia terminatedwith antitachycardia pacing, an arrhythmia terminated with aninternally-applied or externally-applied high energy shock, etc.Detection of an arrhythmia-ending event can be determined viahigh-voltage detection circuitry, or any of a number of sensors fordiscriminating between arrhythmias and for determining rate.

Various embodiments deliver neural stimulation to elicit aparasympathetic response (e.g. stimulate nerve activity at aparasympathetic target and/or inhibit nerve activity at a sympathetictarget). A parasympathetic response, for example, may be desired todecrease myocardial excitability.

For example, neural stimulation that elicits a parasympathetic responsedecreases myocardial excitability and conduction time, thereby reducingthe likelihood of spontaneous recurrence after the arrhythmic-endingevent. Spontaneous recurrence is a particular concern for atrial orsupraventricular arrhythmias. In addition, efficacies of pacingtherapies such as bradycardia pacing and atrial overdrive pacing may beimproved with the decrease of myocardial excitability that results fromthis type of neural stimulation. High-energy antitachycardia shocks maycause major disturbances of parasympathetic and sympathetic activity.For example, shocks may cause a burst of increased sympathetic activity,which may be attributable to the pain associated with the stimulation.Such a sympathetic burst can be pro-arrhythmic, which also suggests thata parasympathetic stimulation response would be appropriate.

A patient may tend toward bradycardia after a shock, which is a reasonto partially or completely withdraw parasympathetic stimulationpost-shock as parasympathetic stimulation also causes the heart rate toslow. Therefore, various embodiments withdraw neural therapies, and/oremploy neural therapies that manage the restoration of properparasympathetic and sympathetic activity and heart rate in response todetection of an arrhythmia-ending event.

Various embodiments deliver neural stimulation to elicit a sympatheticresponse (e.g. stimulate nerve activity at a sympathetic target and/orinhibit nerve activity at a parasympathetic target). A sympatheticresponse, for example, may be desired to increase cardiac output.

Various embodiments use a programmable post-arrhythmia period of timethat allows for multiple programmable post-arrhythmia therapies. Forexample, various embodiments provide post-arrhythmia neural stimulationin response to a non-sustained or self-terminating ventricular episodesuch as a run of PVCs which may require an increase in sympathetic tone.Various embodiments withhold neural stimulation for a brief period afterdetection of a high-energy defibrillation shock followed by neuralstimulation for the remainder of the post-arrhythmia period. Variousembodiments provide post-arrhythmia neural stimulation in conjunctionwith post-arrhythmia bradycardia therapies, where the post-arrhythmianeural stimulation can include the withdrawal of neural stimulation.

Various embodiments provide neural stimulation to suppress excessivesympathetic burst during and just after the shock, followed by a briefwithdrawal of neural stimulation post-shock to prevent excessivebradycardia, which can be associated with a postshock state, and thenfollowed by neural stimulation for the remainder of the post-arrhythmiaperiod. Various embodiments define the post-arrhythmia period in termsof a predetermined duration of time. Predetermined physiologicconditions can be used to define the end of the arrhythmia. For example,any combination of one or more of the following from the atria and/orventricles can be used to determine the end of an arrhythmia: rate,rhythm, conduction (e.g. QRS width), repolarization properties (e.g. QTinterval), etc. Once a specified combination of these parameters returnto normal, the post-arrhythmia period can be considered to have ended.An evoked response (see, for example, U.S. application Ser. No.11/157,244) can also be used to determine the end of an arrhythmia. Theduration can be physician determined or device determined, and thedefinition based on physiologic conditions can be physician determined,physician enabled, device determined or device enabled. The evokedresponse can by physician determined, physician enabled, devicedetermined or device enabled.

Various embodiments deliver neural stimulation therapy in anticipationof or in synchronization to the application of a high-voltageantitachycardia shock. The neural stimulation therapy can be deliveredto provide a neurally-mediated analgesia to reduce the pain associatedwith the shock. The antitachycardia shock can be applied to terminateatrial or ventricular tachycardias.

If neurostimulation therapy is already being applied in the patient, thestimulation parameters are switched between or among stimulation modes(e.g. low-duty-cycle heart failure therapy to high-duty-cycle painmanagement). Various embodiments apply neural stimulation during thetachycardia detection period and/or during ATP application inanticipation of a shock, in response to parameter(s) predictive of ashockable event (VT, T-wave alternans, pulsus alternans, etc.), inresponse to a command from a physician or other care-giver (e.g. aprogrammer command during defibrillation threshold testing), in responseto ischemia detection, in response to a patient trigger (e.g. with anexternal magnet or communicator) as needed (e.g. in response to anginapain, or even non-cardiac pain). Where the device is responsive to apatient trigger, various device embodiments limit the application ofneural stimulation (e.g. a maximum dose in a 24-hour period). A baselinemaintenance dose may be applied, which can then be increased by apatient trigger.

In some embodiments, the neural stimulator and the defibrillator areseparate implantable devices. The neural stimulator can receive a signalfrom the defibrillator in order to trigger the application of neuralstimulation, or can be adapted to automatically detect the applicationof defibrillatory energy (from an internal or external device) andrespond accordingly. In some embodiments, the device does not haveintracardiac leads. Some device embodiments have subcutaneousdefibrillation capabilities. Various embodiments deliver neuralstimulation to treat cardiovascular disease, lower defibrillationthreshold (DFT), and/or provide shock-related analgesia. If interactionis anticipated between neurally-mediated analgesia and pain medications,neural stimulation would be modulated in response to the application ofpain medication. Modulation can occur in response to either a patienttrigger (e.g. magnet or communicator) or a trigger from an electronicpill box, which would communicate wirelessly with the implantabledevice. If different neural stimulation therapies are used to lower DFTand provide shock-related analgesia, then the neural stimulationtherapies can be appropriately multiplexed or synchronized. Ifinteraction is anticipated between the neural stimulation and arrhythmiadetection (by CRM components for example), the neural stimulation can beturned off or switched to a low interference mode when a potentialarrhythmic situation is identified and communicated to the neuralstimulator so detection can proceed without interference.

Illustrated below are therapy time lines. The time lines are not meantto be drawn to any particular scale, but rather are intended toillustrate various operational modes for various embodiments of neuralstimulation systems.

FIG. 1 illustrates a therapy time line where prophylactic neuralstimulation 101A and 101B is interrupted for a temporary neuralstimulation therapy 102, according to various embodiments. In variousembodiments, the temporary neural stimulation includes a neuralstimulation therapy to treat an arrhythmia. In various embodiments, thetemporary neural stimulation includes a neural stimulation therapy totreat apnea. In various embodiments, the temporary neural stimulationincludes a neural stimulation therapy to treat pain, such as therapiesfor migraines, angina, pain associated with antitachycardia shocks, orother pain. The illustrated temporary neural stimulation therapy 102 isinitiated in response to a therapy trigger 103, which can bedevice-initiated, physician-initiated, or patient-initiated. Theprophylactic neural stimulation can be a chronic therapy such as neuralstimulation to provide an anti-remodeling therapy, to control bloodpressure, or to prevent or reduce the risk of cardiac arrhythmia.

FIG. 2 illustrates a therapy time line where pre-therapy andpost-therapy stimulations are delivered, according to variousembodiments of the present subject matter. In various embodiments, thesystem delivers pretherapy 204 in response to a therapy trigger 203. Anexample of pretherapy includes neural stimulation to reduce pain and/orneural stimulation to lower defibrillation threshold in anticipation ofan antitachycardia shock. Another example of pretherapy includes neuralstimulation to change a tachycardia to make it more amenable to anantitachycardia pacing (ATP) therapy (see, for example, U.S. applicationSer. No. 11/382,120, filed May 8, 2006 and entitled METHOD AND DEVICEFOR PROVIDING ANTI-TACHYARRHYTHMIA THERAPY, which is herein incorporatedby reference). Another example of pre-therapy is turning off oradjusting the neural stimulation to avoid the neural stimulation frominterfering with arrhythmia detection After the pretherapy, the systemdelivers therapy 205 which, for example, can be an antitachycardia shockor antitachycardia pacing for various embodiments that treat arrhythmia.After the therapy is completed, as identified by the end of therapytrigger 206, a post-therapy neural stimulation schedule 207 is providedto assist with a physiological recovery from the therapy. In variousembodiments that treat arrhythmia, the post-therapy neural stimulationschedule is provided to reduce the risk of another arrhythmia episodeand/or maintain appropriate cardiac output.

FIG. 3 illustrates a therapy time line where pre-therapy and multi-stagepost-therapy stimulations are delivered, according to variousembodiments. In various embodiments, the system delivers pretherapy 304in response to a therapy trigger 303. An example of pretherapy includesneural stimulation to reduce pain and/or neural stimulation to lowerdefibrillation threshold in anticipation of an antitachycardia shock.Another example of pretherapy includes neural stimulation to change atachycardia to make it more amenable to an antitachycardia pacing (ATP)therapy. Another example of pre-therapy is turning off or adjusting theneural stimulation to avoid the neural stimulation from interfering witharrhythmia detection. After the pretherapy, the system delivers therapy305, which, for example, can be an antitachycardia shock orantitachycardia pacing for various embodiments that treat arrhythmia.After the therapy is completed, as identified by the end of therapytrigger 306, a multistage post-therapy neural stimulation schedule isprovided to assist with a physiological recovery from the therapy. Theillustrated multistage post-therapy neural stimulation schedule includesa first stage 307A and a second stage 307B. Various embodiments turn theneural stimulation off during the first stage 307A.

FIG. 4 illustrates a therapy time line, wherein prophylactic neuralstimulation is interrupted to provide a pre-therapy stimulation, atherapy, and a multi-stage post-therapy stimulation, according tovarious embodiments. The time line illustrated in FIG. 4 is similar toFIG. 3, and further illustrates that prophylactic neural stimulation401A and 401B is interrupted by pretherapy neural stimulation 404, atherapy 405, first and second stages 407A and 407B of post therapyneural stimulation. The illustrated time line indicates that the systemis responsive to a therapy trigger 403 and an end of therapy trigger406.

FIG. 5 illustrates a therapy time line where a post-arrhythmia therapyis delivered, according to various embodiments. In the illustratedembodiment, the system responds to an end of an arrhythmia trigger 506with a temporary neural stimulation therapy for arrhythmia recovery 507.Various embodiments detect the end of an arrhythmia by receiving acommunication signal from the defibrillator indicating that a shock isbeing applied, or by detecting shock energy from the appliedanti-tachyarrhythmia shock. Various embodiments wait an intershockperiod to ensure that the shock was successful and thus determine thatthe arrhythmia has ended. The temporary neural stimulation therapy 507can include a time for withdrawing some or all parasympatheticstimulation to avoid encouraging a bradycardia episode after the shock,or can include applying neural stimulation to elicit some sympatheticstimulation to promote cardiac output immediately after the shock. Thetemporary neural stimulation therapy 507 can include neural stimulationto elicit a parasympathetic response to discourage another arrhythmicepisode after the therapy is applied.

FIG. 6 illustrates a therapy time line where prophylactic neuralstimulation is interrupted by post-arrhythmia therapy, according tovarious embodiments. The time line illustrated in FIG. 6 is similar tothe time line illustrated FIG. 5, and further illustrates thatprophylactic neural stimulation 601A and 601B is interrupted by an endof arrhythmia trigger 606 for the application of the temporary neuralstimulation therapy 607 for arrhythmia recovery.

FIG. 7 illustrates a therapy time line where a multi-stagepost-arrhythmia therapy is delivered, according to various embodiments.The time line illustrated in FIG. 7 is similar to the time lineillustrated in FIG. 5, and further illustrates that the neuralstimulation delivered after the arrhythmia 706 includes a first stage707A and a second stage 707B. The neural stimulation therapy, if any, inthe first stage 707A after the arrhythmia is distinct from the neuralstimulation therapy in the second stage 707B after the arrhythmia. Twostages are illustrated for the post-arrhythmia therapy in FIG. 7, butadditional stages can be implemented as appropriate to produce thedesired effects from the neural stimulation. For example, the firststage may turn off or reduce neural stimulation that elicits aparasympathetic response to prevent bradycardia, and the second stagemay deliver neural stimulation to elicit a parasympathetic response toprevent re-initiation of the arrhythmia. Or, for example, the firststage may deliver neural stimulation to elicit a parasympatheticresponse to prevent re-initiation of the arrhythmia, and the secondstage may turn off or reduce neural stimulation that elicits aparasympathetic response to prevent bradycardia.

FIG. 8 illustrates a therapy time line where prophylactic neuralstimulation is interrupted by multi-stage post-arrhythmia therapy,according to various embodiments. The time line illustrated in FIG. 8 issimilar to the time line illustrated FIG. 7, and further illustratesthat prophylactic neural stimulation 801A and 801B is interrupted by anend of arrhythmia trigger 806 for the application of the temporary,multi-stage neural stimulation therapy 807A and 807B for arrhythmiarecovery.

FIG. 9 illustrates a therapy time line where prophylactic neuralstimulation 901A and 901B is interrupted by a detected arrhythmia 903 todeliver a pre-therapy stimulation 904, a therapy 905 for an arrhythmia,and a multi-stage post arrhythmia stimulation 907A and 907B deliveredafter the end of the arrhythmia 906, according to various embodiments.Examples of pretherapy neural stimulation include neural stimulation toreduce pain associated with the therapy, to lower a defibrillationthreshold, or to modify a tachyarrhythmia in anticipation for anantitachycardia pacing therapy. Therapies for arrhythmias can includeneural stimulation to treat the arrhythmia, antitachycardia pacing,and/or antitachycardia shocks. The illustrated first stage ofpost-arrhythmia stimulation involves partially or completely withdrawingneural stimulation, such as stimulation that may induce aparasympathetic response after the therapy (e.g. shock) to discouragebradycardia episodes. The illustrated second stage of post-arrhythmiastimulation involves delivering neural stimulation according to aschedule to discourage another tachycardia for a period in which theheart is more vulnerable to subsequent tachycardias. The triggerindicating the end of the arrhythmia 906 can be sensed (e.g. a sensednormal sinus rhythm, a sensed antitachycardia shock plus an intershockperiod) or can be communicated through a communication signal. Inembodiments that are capable of delivering simultaneous therapies (e.g.neural stimulation, antitachycardia pacing, and shock), the controllercan be programmed to prevent the delivery of simultaneous energydischarges (see, for example, US 20060241699, entitled NeuralStimulation System To Prevent Simultaneous Energy Discharges).

FIG. 10 illustrates a flow diagram of a process for deliveringpost-arrhythmia vagus nerve modulation (VNM), according to variousembodiments. The illustrated process includes a normal or chronic VNM at1008. After an arrhythmia has ended, the process proceeds to temporarilydeliver a post-arrhythmia VNM at 1009. In the illustrated embodiment,the process returns to 1008 once a timeout is received for thepost-arrhythmia VNM therapy.

FIG. 11 illustrates a flow diagram of a process for deliveringpost-arrhythmia vagus nerve modulation (VNM), according to variousembodiments. The illustrated process includes a normal or chronic VNM at1108. VNM can also be referred to as vagal stimulation therapy (VST).After an arrhythmia has ended, the process proceeds to 1110 to determinehow the arrhythmia terminated (e.g. a self-terminating or non-sustainedarrhythmia, a low voltage terminated arrhythmia, or a high-voltageterminated arrhythmia). A VNM therapy for non-sustained orself-terminating arrhythmias is delivered at 1111, a VNM therapy forarrhythmias terminated using low voltage stimulation is delivered at1112, and a VNM therapy for arrhythmias terminated using high-voltagestimulation shocks is delivered at 1113. After the VNM therapy, theprocess returns to 1108 after a timeout or terminating event, such as acommunicated signal from a CRM device or a physiologic signal.

FIG. 12 illustrates a flow diagram of a process for deliveringpost-arrhythmia vagus nerve modulation (VNM), according to variousembodiments. The illustrated process includes a normal or chronic VNM at1208, along with normal bradycardia therapies. After an arrhythmia hasended, the process proceeds to 1210 to determine how the arrhythmiaterminated (e.g. a self-terminating or non-sustained arrhythmia, a lowvoltage terminated arrhythmia, or a high-voltage terminated arrhythmia).A VNM therapy for non-sustained or self-terminating atrial arrhythmiasis delivered at 1211A along with an atrial bradycardia therapy, and aVNM therapy for non-sustained or self-terminating ventriculartachyarrhythmias is delivered at 1211B along with a ventriculartachyarrhythmia bradycardia therapy. A VNM therapy for arrhythmiasterminated using low voltage. ATP stimulation is delivered at 1212 alongwith post-ATP bradycardia therapies, and a VNM therapy for arrhythmiasterminated using high-voltage antitachycardia stimulation shocks isdelivered at 1213 along with post-shock bradycardia therapies. Inresponse to a timeout or terminating event, normal VNM therapies can bedelivered again. In the illustrated embodiment, the post-shock VNMtherapies includes temporarily withdrawing VNM (e.g. for a time periodon the order of seconds) at 1214 until a stage 1 timeout is received andincludes applying a post-shock VNM (e.g. for a time period on the orderof minutes) at 1215 until a stage 2 timeout is received, upon which timenormal VNM therapies are delivered at 1208.

FIG. 13 illustrates a flow diagram of a process for deliveringpost-arrhythmia vagus nerve modulation (VNM), according to variousembodiments. The illustrated process includes a normal or chronic VNM at1308, along with normal bradycardia therapies. After an arrhythmia hasended, the process proceeds to 1310 to determine how the arrhythmiaterminated (e.g. a self-terminating or non-sustained arrhythmia, a lowvoltage terminated arrhythmia, or a high-voltage terminated arrhythmia).A VNM therapy for non-sustained or self-terminating atrial arrhythmiasis delivered at 1311A along with an atrial bradycardia therapy, and aVNM therapy for non-sustained or self-terminating ventriculartachyarrhythmias is delivered at 1311B along with a ventriculartachyarrhythmia bradycardia therapy. A VNM therapy for arrhythmiasterminated using low voltage, ATP stimulation is delivered at 1312 alongwith post-ATP bradycardia therapies, and a VNM therapy for arrhythmiasterminated using high-voltage antitachycardia stimulation shocks isdelivered at 1313 along with post-shock bradycardia therapies. In theillustrated embodiment, the process responds to a stage 1 timeout byapplying post-arrhythmia VNM therapy and post-arrhythmia brady therapyat 1316 until a stage 2 timeout is received, at which time normal VNMtherapies and normal brady therapies are delivered at 1308.

FIG. 14 illustrates an implantable medical device (IMD) 1420, accordingto various embodiments. The illustrated IMD 1420 provides neuralstimulation signals for delivery to predetermined neural targets toprovide a desired therapy. The illustrated device includes controllercircuitry 1421 and memory 1422. The controller circuitry is capable ofbeing implemented using hardware, software, and combinations of hardwareand software. For example, according to various embodiments, thecontroller circuitry includes a processor to perform instructionsembedded in the memory to perform functions associated with the neuralstimulation therapy. The illustrated device further includes atransceiver 1423 and associated circuitry for use to communicate with aprogrammer or another external or internal device. Various embodimentshave wireless communication capabilities. For example, some transceiverembodiments use a telemetry coil to wirelessly communicate with aprogrammer or another external or internal device.

The illustrated device further includes a therapy delivery system 1424,including neural stimulation circuitry. Various embodiments of thedevice also includes sensor circuitry 1425. According to someembodiments, one or more leads are able to be connected to the sensorcircuitry and neural stimulation circuitry. Some embodiments usewireless connections between the sensor(s) and sensor circuitry, andsome embodiments use wireless connections between the stimulatorcircuitry and electrodes. According to various embodiments, the neuralstimulation circuitry is used to apply electrical stimulation pulses todesired neural targets, such as through one or more stimulationelectrodes 1426 positioned at predetermined location(s). Someembodiments use transducers to provide other types of energy, such asultrasound, light or magnetic energy. In various embodiments, the sensorcircuitry is used to detect physiological responses. Examples ofphysiological responses include blood pressure, cardiac activity such asheart rate, and respiration such as tidal volume and minute ventilation.The controller circuitry can control the therapy using a therapyschedule in memory 1422 and an internal clock or timer 1427, or cancompare a target range (or ranges) of the sensed physiologicalresponse(s) stored in the memory 1422 to the sensed physiologicalresponse(s) to appropriately adjust the intensity of the neuralstimulation/inhibition.

According to various embodiments using neural stimulation, thestimulation circuitry 1424 is adapted to set or adjust any one or anycombination of stimulation features. Examples of stimulation featuresinclude, but are not limited to, the amplitude, frequency, polarity andwave morphology of the stimulation signal. Examples of wave morphologyinclude a square wave, triangle wave, sinusoidal wave, and waves withdesired harmonic components to mimic white noise such as is indicativeof naturally-occurring nerve traffic. Some embodiments of the neuralstimulation circuitry 1424 are adapted to generate a stimulation signalwith a predetermined amplitude, morphology, pulse width and polarity,and are further adapted to respond to a control signal from thecontroller to modify at least one of the amplitude, wave morphology,pulse width and polarity. Some embodiments of the neural stimulationcircuitry 1424 are adapted to generate a stimulation signal with apredetermined frequency, and are further adapted to respond to a controlsignal from the controller to modify the frequency of the stimulationsignal.

The controller 1421 can be programmed to control the neural stimulationdelivered by the stimulation circuitry 1424 according to stimulationinstructions, such as a stimulation schedule, stored in the memory 1422.Neural stimulation can be delivered in a stimulation burst, which is atrain of stimulation pulses at a predetermined frequency. Stimulationbursts can be characterized by burst durations and burst intervals. Aburst duration is the length of time that a burst lasts. A burstinterval can be identified by the time between the start of successivebursts. A programmed pattern of bursts can include any combination ofburst durations and burst intervals. A simple burst pattern with oneburst duration and burst interval can continue periodically for aprogrammed period or can follow a more complicated schedule. Theprogrammed pattern of bursts can be more complicated, composed ofmultiple burst durations and burst interval sequences. The programmedpattern of bursts can be characterized by a duty cycle, which refers toa repeating cycle of neural stimulation ON for a fixed time and neuralstimulation OFF for a fixed time.

According to some embodiments, the controller 1421 controls the neuralstimulation generated by the stimulation circuitry by initiating eachpulse of the stimulation signal. In some embodiments, the controllercircuitry initiates a stimulation signal pulse train, where thestimulation signal responds to a command from the controller circuitryby generating a train of pulses at a predetermined frequency and burstduration. The predetermined frequency and burst duration of the pulsetrain can be programmable. The pattern of pulses in the pulse train canbe a simple burst pattern with one burst duration and burst interval orcan follow a more complicated burst pattern with multiple burstdurations and burst intervals. In some embodiments, the controller 1421controls the stimulation circuitry 1424 to initiate a neural stimulationsession and to terminate the neural stimulation session. The burstduration of the neural stimulation session under the control of thecontroller 1421 can be programmable. The controller may also terminate aneural stimulation session in response to an interrupt signal, such asmay be generated by one or more sensed parameters or any other conditionwhere it is determined to be desirable to stop neural stimulation.

The sensor circuitry is used to detect a physiological response. Thecontroller 1421 compares the response to a target range stored inmemory, and controls the neural stimulation based on the comparison inan attempt to keep the response within the target range. The targetrange can be programmable.

The illustrated device includes a clock or timer 1427 which can be usedto execute the programmable stimulation schedule. For example, aphysician can program a daily schedule of therapy based on the time ofday. A stimulation session can begin at a first programmed time, and canend at a second programmed time. Various embodiments initiate and/orterminate a stimulation session based on a signal triggered by a user.Various embodiments use sensed data to enable and/or disable astimulation session. The timer can control the duration of pre-therapy,therapy, post-therapy, and therapy recovery neural stimulation stages.

According to various embodiments, the schedule refers to the timeintervals or period when the neural stimulation therapy is delivered. Aschedule can be defined by a start time and an end time, a start timeand a duration, a start time and a terminating triggering event, or aninitiating triggering event and an end time, or a duration or aterminating triggering event. Various schedules deliver therapyperiodically. According to various embodiments, the device is programmedwith a therapy schedule before, during and/or after arrhythmias, asdiscussed above.

According to some examples that provide prophylactic neural stimulation,a device can be programmed with a therapy schedule to deliver therapyfrom midnight to 2 AM every day, or to deliver therapy for one hourevery six hours, or to delivery therapy for two hours per day, oraccording to a more complicated timetable. Various device embodimentsapply the therapy according to the programmed schedule contingent onenabling conditions, such as patient rest or sleep, low heart ratelevels, and the like. The therapy schedule can also specify how thestimulation is delivered, such as continuously at the pulse frequencythroughout the identified therapy period (e.g. 5 Hz pulse frequency forone hour during the delivery period), or according to a defined dutycycle during the therapy delivery period (e.g. 10 seconds per minute at5 Hz pulse frequency for one hour per day). As illustrated by theseexamples, the therapy schedule is distinguishable from the duty cycle.

FIG. 15 illustrates an implantable medical device (IMD) 1528 having aneural stimulation (NS) component 1529 and a cardiac rhythm management(CRM) component 1530 according to various embodiments. The illustrateddevice includes a controller 1531 and memory 1532. According to variousembodiments, the controller includes hardware, software, or acombination of hardware and software to perform the neural stimulationand CRM functions. For example, the programmed therapy applicationsdiscussed in this disclosure may be stored as computer-readableinstructions embodied in memory and executed by a processor. Forexample, therapy schedule(s) and programmable parameters can be storedin memory. According to various embodiments, the controller includes aprocessor to execute instructions embedded in memory to perform theneural stimulation and CRM functions. Various embodiments include CRMtherapies such as bradycardia pacing, antitachycardia therapies such asATP, defibrillation and cardioversion, and cardiac resynchronizationtherapy (CRT). The illustrated device further includes a transceiver1533 and associated circuitry for use to communicate with a programmeror another external or internal device. Various embodiments include atelemetry coil.

The CRM therapy section 1530 includes components, under the control ofthe controller, to stimulate a heart and/or sense cardiac signals usingone or more electrodes. The illustrated CRM therapy section includes apulse generator 1534 for use to provide an electrical signal through anelectrode to stimulate a heart, and further includes sense circuitry1535 to detect and process sensed cardiac signals. An interface 1536 isgenerally illustrated for use to communicate between the controller 1531and the pulse generator 1534 and sense circuitry 1535. Three electrodesare illustrated as an example for use to provide CRM therapy. However,the present subject matter is not limited to a particular number ofelectrodes or electrode sites. Each electrode may have its own pulsegenerator and sense circuitry. However, the present subject matter isnot so limited. A signal pulse generating and sensing function can bemultiplexed to function with multiple electrodes. Additionally, anelectrode can be multiplexed to function with more than one pulsegenerating and sensing function.

The NS therapy section 1529 includes components, under the control ofthe controller, to stimulate a neural stimulation target and/or senseparameters associated with nerve activity or surrogates of nerveactivity such as blood pressure and respiration. Three interfaces 1537are illustrated for use to provide neural stimulation. However, thepresent subject matter is not limited to a particular number interfaces,or to any particular stimulating or sensing functions. Pulse generators1538 are used to provide electrical pulses to transducer or transducersfor use to stimulate a neural stimulation target. According to variousembodiments, the pulse generator includes circuitry to set, and in someembodiments change, the amplitude of the stimulation pulse, thefrequency of the stimulation pulse, the burst frequency of the pulse,and the morphology of the pulse such as a square wave, triangle wave,sinusoidal wave, and waves with desired harmonic components to mimicwhite noise or other signals. Sense circuits 1539 are used to detect andprocess signals from a sensor, such as a sensor of nerve activity, heartrate, blood pressure, respiration, and the like. The interfaces 1537 aregenerally illustrated for use to communicate between the controller 1531and the pulse generator 1538 and sense circuitry 1539. Each interface,for example, may be used to control a separate lead. Various embodimentsof the NS therapy section only include a pulse generator to stimulate aneural target. The illustrated device further includes a clock/timer1540, which can be used to deliver the programmed therapy according to aprogrammed stimulation protocol and/or schedule.

FIG. 16 shows a system diagram of an embodiment of amicroprocessor-based implantable device, according to variousembodiments. The controller of the device is a microprocessor 1641 whichcommunicates with a memory 1642 via a bidirectional data bus. Thecontroller could be implemented by other types of logic circuitry (e.g.,discrete components or programmable logic arrays) using a state machinetype of design. As used herein, the term “circuitry” should be taken torefer to either discrete logic circuitry or to the programming of amicroprocessor. Shown in the figure are three examples of sensing andpacing channels designated “A” through “C” comprising bipolar leads withring electrodes 1643A-C and tip electrodes 1644A-C, sensing amplifiers1645A-C, pulse generators 1646A-C, and channel interfaces 1647A-C. Eachchannel thus includes a pacing channel made up of the pulse generatorconnected to the electrode and a sensing channel made up of the senseamplifier connected to the electrode. The channel interfaces 1647A-Ccommunicate bidirectionally with the microprocessor 1641, and eachinterface may include analog-to-digital converters for digitizingsensing signal inputs from the sensing amplifiers and registers that canbe written to by the microprocessor in order to output pacing pulses,change the pacing pulse amplitude, and adjust the gain and thresholdvalues for the sensing amplifiers. The sensing circuitry of thepacemaker detects a chamber sense, either an atrial sense or ventricularsense, when an electrogram signal (i.e., a voltage sensed by anelectrode representing cardiac electrical activity) generated by aparticular channel exceeds a specified detection threshold. Pacingalgorithms used in particular pacing modes employ such senses to triggeror inhibit pacing. The intrinsic atrial and/or ventricular rates can bemeasured by measuring the time intervals between atrial and ventricularsenses, respectively, and used to detect atrial and ventriculartachyarrhythmias.

The electrodes of each bipolar lead are connected via conductors withinthe lead to a switching network 1648 controlled by the microprocessor.The switching network is used to switch the electrodes to the input of asense amplifier in order to detect intrinsic cardiac activity and to theoutput of a pulse generator in order to deliver a pacing pulse. Theswitching network also enables the device to sense or pace either in abipolar mode using both the ring and tip electrodes of a lead or in aunipolar mode using only one of the electrodes of the lead with thedevice housing (can) 1649 or an electrode on another lead serving as areturn electrode. A shock pulse generator 1650 is also interfaced to thecontroller for delivering an antitachycardia shock using shockelectrodes 1651 and 1652 to the atria or ventricles upon detection of ashockable tachyarrhythmia.

Neural stimulation channels, identified as channels D and E, areincorporated into the device for delivering neural stimulation to elicita parasympathetic response (stimulate parasympathetic traffic and/orinhibit sympathetic traffic) and/or neural stimulation to elicit asympathetic response (stimulate sympathetic traffic and/or inhibitparasympathetic traffic), where one illustrated channel includes abipolar lead with a first electrode 1653D and a second electrode 1654D,a pulse generator 1655D, and a channel interface 1656D, and the otherillustrated channel includes a bipolar lead with a first electrode 1653Eand a second electrode 1654E, a pulse generator 1655E, and a channelinterface 1656E. Other embodiments may use unipolar leads in which casethe neural stimulation pulses are referenced to the can or anotherelectrode. The pulse generator for each channel outputs a train ofneural stimulation pulses which may be varied by the controller as toamplitude, frequency, duty-cycle, and the like. In this embodiment, eachof the neural stimulation channels uses a lead which can beintravascularly disposed near an appropriate neural target. Other typesof leads and/or electrodes may also be employed. A nerve cuff electrodemay be used in place of an intravascularly disposed electrode to provideneural stimulation. In some embodiments, the leads of the neuralstimulation electrodes are replaced by wireless links. The figureillustrates a telemetry interface 1657 connected to the microprocessor,which can be used to communicate with an external device. Theillustrated microprocessor 1641 is capable of performing neuralstimulation (NS) therapy routines and myocardial (CRM) stimulationroutines.

FIG. 17 illustrates a system embodiment in which an IMD 1758 is placedsubcutaneously or submuscularly in a patient's chest with a lead 1759positioned to stimulate a vagus nerve. According to various embodiments,the neural stimulation lead 1759 is subcutaneously tunneled to a neuraltarget, and has a nerve cuff electrode to stimulate the neural target.Some vagus nerve stimulation lead embodiments are intravascularly fedinto a vessel proximate to the neural target, and use electrode(s)within the vessel to transvascularly stimulate the neural target. Forexample, some embodiments stimulate the vagus using electrode(s)positioned within the internal jugular vein. Other embodiments deliverneural stimulation to the neural target from within the trachea, thelaryngeal branches of the internal jugular vein, and the subclavianvein. The neural targets can be stimulated using other energy waveforms,such as ultrasound and light energy waveforms. Other neural targets canbe stimulated, such as baroreceptors, cardiac nerves and cardiac fatpads. The illustrated system includes leadless ECG electrodes on thehousing of the device. These ECG electrodes 1760 are capable of beingused to detect heart rate, a specific arrhythmic episode, or arrhythmiatreatment, for example.

FIG. 18 illustrates a system embodiment that includes an implantablemedical device (IMD) 1858 with satellite electrode(s) 1859 positioned tostimulate at least one neural target. The satellite electrode(s) areconnected to the Imp, which functions as the planet for the satellites,via a wireless link. Stimulation and communication can be performedthrough the wireless link. Examples of wireless links include RF linksand ultrasound links. Examples of satellite electrodes includesubcutaneous electrodes, nerve cuff electrodes and intravascularelectrodes. Various embodiments include satellite neural stimulationtransducers used to generate neural stimulation waveforms such asultrasound and light waveforms. The illustrated system includes leadlessECG electrodes on the housing of the device. These ECG electrodes 1860are capable of being used to detect heart rate, a specific arrhythmicepisode or arrhythmia treatment, for example.

FIG. 19 illustrates an IMD 1958 placed subcutaneously or submuscularlyin a patient's chest with lead(s) 1961 positioned to provide a CRMtherapy to a heart, and with a lead 1959 positioned to stimulate and/orinhibit neural traffic at a neural target, such as a vagus nerve,according to various embodiments. According to various embodiments,neural stimulation lead(s) are subcutaneously tunneled to a neuraltarget, and can have a nerve cuff electrode to stimulate the neuraltarget. Some lead embodiments are intravascularly fed into a vesselproximate to the neural target, and use transducer(s) within the vesselto transvascularly stimulate the neural target. For example, someembodiments target the vagus nerve using electrode(s) positioned withinthe internal jugular vein.

FIG. 20 illustrates an IMD 2058 with lead(s) 2061 positioned to providea CRM therapy to a heart, and with satellite transducers 2059 positionedto stimulate/inhibit a neural target such as a vagus nerve, according tovarious embodiments. The satellite transducers are connected to the IMD,which functions as the planet for the satellites, via a wireless link.Stimulation and communication can be performed through the wirelesslink. Examples of wireless links include RF links and ultrasound links.Although not illustrated, some embodiments perform myocardialstimulation using wireless links. Examples of satellite transducersinclude subcutaneous electrodes, nerve cuff electrodes and intravascularelectrodes.

FIG. 21 illustrates an embodiment of a responsive relationship of an IMDcontroller to a triggering event. The illustration includes a controller2180 adapted to operate the IMD in a number of modes 2181 including afirst mode, a second mode and an Nth mode. The illustration furtherincludes a representation of a triggering event 2182, which can be anautomatic event and/or a patient-actuated event such as a magnet movedproximate to arced switch or a patient-actuated programmer. Automatictriggering events can also include a detected physiologic change such asa detected change in heart rate, a detected arrhythmia, a detectedchange in a respiratory rate and a detected change in blood pressure.Automatic triggering also includes detecting electrical pulses, such ashigh energy defibrillation shocks, trains of high frequency ATP pulses,or bradycardia therapy pacing pulses. Such pulses can be detectedthrough, for example, leadless ECG electrodes. The illustration alsoincludes an enable signal 2183 connected to the controller to enable amode of operation via a switch 2184. The triggering event is adapted tocontrol the switch to selectively enable a mode of operation by thecontroller. The illustrated responsive relationship can be performed inhardware, software, or a combination thereof. Sensor and/or telemetrysignals can be used to provide the triggering event. The illustrateddevice includes a clock/timer, which can be used to receive a SET signalfrom the mode selector, and send a timeout signal to the mode selectorafter a predetermined period of time. The illustrated device alsoincludes a memory which can include a therapy schedule for the modeselector, and parameters for the various modes.

FIG. 22 illustrates an embodiment of a controller 2262 capable ofswitching modes within a set of operation modes 2271, a set ofstimulation site modes 2272, and a set of feedback modes 2273. Withrespect to the set of operation modes, the illustrated controller isadapted to switch between or among two or more modes. Examples of modeswithin the set of operation modes includes a stimulation and sensingmode in which closed-loop neural stimulation is provided to neuraltarget(s) based on sensed parameters, a stimulation mode in whichopen-loop neural stimulation is provided to neural target(s), and asensing mode in which neural stimulation is not provided to neuraltarget(s) but sensing processes continue. Examples of sensed parametersinclude, but are not limited to, blood pressure, heart rate, and nervetraffic.

With respect to the set of stimulation site modes, the illustratedcontroller 2262 is adapted to switch between or among two or morestimulation site modes. Examples of applications for switchingstimulation site modes includes switching between parasympathetic andsympathetic nerve stimulation, switching from afferent to efferentstimulation, and changing the dose of the neural stimulation therapy bychanging the number of stimulation sites. For example, the illustratedcontroller is adapted to switch among a mode to stimulate a firststimulation site or sites, a mode to stimulate a second stimulation siteor sites, and a mode to stimulate an Nth stimulation site or sites. Thesame stimulation site can be used to inhibit or stimulate nerve trafficusing different stimulation parameters, or can be used to stimulatenerve traffic in the efferent direction, in the afferent direction, orin both the efferent and afferent direction.

With respect to the set of feedback modes, the illustrated controller isadapted to switch among sensing site modes 2274 and to switch amongsensed parameter and/or composite parameter modes 2275. Compositeparameters are parameters based on two or more other parameters.Examples of applications for switching among sensing site modes includesrecording parasympathetic or sympathetic traffic, recording afferent orefferent traffic, and switching from atrial to ventricular rhythmmonitoring. Examples of applications for switching among sensedparameter/composite parameter modes include detecting short-term briefevents such as an impulse burst versus a time-averaged long-term signaltrend, and detecting impulse duration versus impulse magnitude. Theillustrated controller is adapted to switch among a first site, a secondsite and an Nth site from which to provide sensing for a feedbacksignal, and is also adapted to switch among a first sensed parameter, asecond sensed parameter and an Nth sensed parameter. Thus, although thesensing site may not change, a different parameter can be detected.

With respect to the set of therapy modes 2276, the illustratedcontroller is adapted to switch between or among two or more modes.Examples of modes within the set of therapy modes includes a neuralstimulation therapy mode, a cardiac rhythm management and/or cardiacresynchronization therapy (CRM/CRT) mode, a neural stimulation and CRMtherapy mode, a drug therapy mode, a neural stimulation and drug therapymode, a CRM/CRT and drug therapy mode, and a neural stimulation, CRM/CRTand drug therapy mode. An example of a neural stimulation mode includesan anti-remodeling, vagal nerve stimulation therapy. An example of aCRM/CRT therapy includes a resynchronization therapy for a heart failurepatient to improve the pumping function of the left ventricle. Examplesof a neural stimulation and a CRM/CRT therapy include a vagal nervestimulation therapy and antitachycardia pacing to terminate arrhythmia,and vagal nerve stimulation in anticipation of a defibrillation shock toreduce the defibrillation threshold. An example of a drug therapy modeincludes an angiogenic growth factor release to treat ischemia. Anexample of a neural stimulation and a drug therapy mode includes vagalnerve stimulation and delivery of an angiogenic drug to promote cardiacmuscle repair after an myocardial infarction. An example of a CRM/CRTand drug therapy includes pacing to unload a region of a heart damagedby a myocardial infarction such that the damaged heart region works lessand delivery of an angiogenic drug to promote cardiac muscle repair. Anexample of a neural stimulation, CRM/CRM and drug therapy includes vagalnerve stimulation, pacing to unload a region of a heart damaged by amyocardial infarction, and delivery of an angiogenic drug to preventpost myocardial infarction remodeling. The illustrated neuralstimulation therapies can be selected among pain therapy, apnea therapy,arrhythmia pre-therapy, arrhythmia therapy, arrhythmia post-therapy(stage 1, 2 . . . N), anti-bradycardia therapy, anti-arrhythmia therapy,anti-hypertension, anti-remodeling therapy, or other therapy. Therapyintensity 2277 is used to select whether the therapy is on or off, or toadjust the intensity of the therapy.

One of ordinary skill in the art will understand that, the modules andother circuitry shown and described herein can be implemented usingsoftware, hardware, and combinations of software and hardware. As such,the terms module and circuitry are intended to encompass softwareimplementations, hardware implementations, and software and hardwareimplementations.

The methods illustrated in this disclosure are not intended to beexclusive of other methods within the scope of the present subjectmatter. Those of ordinary skill in the art will understand, upon readingand comprehending this disclosure, other methods within the scope of thepresent subject matter. The above-identified embodiments, and portionsof the illustrated embodiments, are not necessarily mutually exclusive.These embodiments, or portions thereof, can be combined. In variousembodiments, the methods are implemented using a computer data signalembodied in a carrier wave or propagated signal, that represents asequence of instructions which, when executed by a processor cause theprocessor to perform the respective method. In various embodiments, themethods are implemented as a set of instructions contained on acomputer-accessible medium capable of directing a processor to performthe respective method. In various embodiments, the medium is a magneticmedium, an electronic medium, or an optical medium.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. Other embodiments will beapparent to those of skill in the art upon reading and understanding theabove description. The scope of the invention should, therefore, bedetermined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

What is claimed is:
 1. A method, comprising: chronically performing aprophylactic neural stimulation therapy; in response to a therapytrigger, delivering an arrhythmia therapy, wherein delivering the othertherapy includes temporarily delivering therapeutic neural stimulationas part of the other therapy; determining when an arrhythmia hasterminated, and responding to termination of the arrhythmia byinitiating a post-therapy neural stimulation that has a programmedduration, wherein stimulation in the post-therapy neural stimulation isdistinct from stimulation in the prophylactic neural stimulationtherapy; and upon completion of the other therapy, chronicallyperforming the prophylactic neural stimulation therapy.
 2. The method ofclaim 1, wherein the prophylactic neural stimulation therapy includeschronically performing the prophylactic neural stimulation according toa programmed therapy schedule contingent on enabling conditions.
 3. Themethod of claim 1, further comprising delivering pre-therapy neuralstimulation, wherein stimulation in the pre-therapy neural stimulationis distinct from stimulation in the prophylactic neural stimulationtherapy.
 4. The method of claim 1, wherein temporarily delivering neuralstimulation includes temporarily delivering a multi-stage therapy. 5.The method of claim 1, wherein temporarily delivering neural stimulationincludes delivering a programmed neural stimulation as a programmedresponse to the therapy trigger.
 6. The method of claim 1, wherein theprophylactic neural stimulation therapy includes neural stimulation tocontrol blood pressure.
 7. The method of claim 1, wherein theprophylactic neural stimulation therapy includes neural stimulation toprevent or reduce a risk of cardiac arrhythmia.
 8. The method of claim1, wherein the prophylactic neural stimulation therapy includes a heartfailure therapy.
 9. The method of claim 1, further comprising: inresponse to a therapy trigger, delivering a pretherapy neuralstimulation in preparation for delivering the other therapy; and uponcompletion of the other therapy, delivering a post-therapy neuralstimulation to assist with recovering from the other therapy.
 10. Themethod of claim 9, wherein delivering a post-therapy neural stimulationincludes delivering the post-therapy neural stimulation using a firststage of stimulation and then using a second stage of stimulationdistinct from the first stage.
 11. The method of claim 9, whereindelivering the pretherapy neural stimulation includes delivering aprogrammed pretherapy neural stimulation having a programmed durationand including a plurality of neural stimulation pulses, wherein thepretherapy neural stimulation is a programmed response to the therapytrigger.
 12. The method of claim 9, further comprising detecting anarrhythmia, and providing the therapy trigger in response to detectingthe arrhythmia.
 13. The method of claim 12, wherein the therapyincludes; an anti-arrhythmia shock therapy, and the pretherapy neuralstimulation includes a neural stimulation therapy to reduce painassociated with the antiarrhythmia shock therapy; or an antitachycardiapacing, and the pretherapy neural stimulation includes a neuralstimulation therapy to modify the arrhythmia in preparation forantitachycardia pacing.
 14. A method, comprising: chronically performinga prophylactic neural stimulation therapy; in response to a therapytrigger, temporarily delivering neural stimulation as part of anarrhythmia therapy, determining when an arrhythmia has terminated, andresponding to termination of the arrhythmia by initiating and deliveringa post-therapy neural stimulation, the post-therapy neural stimulationhaving a programmed duration and is distinct from the prophylacticneural stimulation therapy; and upon completion of the arrhythmiatherapy, chronically performing the prophylactic neural stimulationtherapy.
 15. The method of claim 14, wherein the chronically-performedprophylactic neural stimulation therapy includes neural stimulation tocontrol blood pressure.
 16. The method of claim 14, wherein thechronically-performed prophylactic neural stimulation therapy includesneural stimulation to prevent or reduce a risk of cardiac arrhythmia.17. The method of claim 14, wherein the chronically-performedprophylactic neural stimulation therapy includes a heart failuretherapy.
 18. The method of claim 14, wherein in response to the therapytrigger, delivering a pretherapy neural stimulation and then deliveringthe arrhythmia therapy.